Clinical correlates of circulating cell-free DNA tumor fraction.
Level 3 - non-randomized controlled study
Multicenter observational cohort study with independent validation cohort
PubMed 34432811 · doi:10.1371/journal.pone.0256436
What was done
Circulating tumor fraction from cell-free DNA was measured in blood samples from patients with breast, lung, and colorectal cancer in the first substudy of the multicenter Circulating Cell-free Genome Atlas study (CCGA; NCT02889978). Linear regression models evaluated relationships between tumor fraction and clinical covariates, including tumor size combined with mitotic activity (tumor mitotic volume based on Ki-67) or metabolic activity (excessive lesion glycolysis based on PET SUV minus 1.0), histologic type, histologic grade, and lymph node status. Models were subsequently validated in a cohort from the second CCGA substudy.
What was found
The abstract does not report specific numerical values, sample sizes, or effect estimates. It reports that for breast and lung cancer, tumor mitotic volume and excessive lesion glycolysis were the only statistically significant covariates associated with tumor fraction. For colorectal cancer, the surface area of tumors invading beyond the subserosa was the only significant covariate.
Why it matters
These findings suggest that cell-free DNA shedding is driven by proliferative aggressiveness and invasive depth rather than tumor size alone, explaining why multi-cancer early detection tests may be most sensitive for faster-growing, aggressive malignancies.
Limits
The abstract reports no participant counts, effect sizes, confidence intervals, or p-values. Analysis is restricted to three solid tumor types, limiting generalizability to other cancers. Retrospective modeling from an observational atlas may be subject to residual confounding.
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